Correlation of Saliva Codeine Concentrations with Plasma Concentrations after Oral Codeine Administration

Abstract

A clinical study was designed to determine if there was a predictable relationship between saliva and plasma codeine concentrations. Drug-free volunteers (n = 17) were administered a 30-mg dose of liquid codeine phosphate. Plasma and saliva specimens were collected at various times for 24 h after administration. Plasma and saliva were analyzed for codeine and morphine by positive-ion chemical ionization gas chromatography-mass spectrometry. The plasma codeine concentrations peaked between 30 min and 2 h after administration and ranged from 19 to 74 ng/mL with a mean of 46 ng/mL. Despite decontamination procedures, elevated saliva codeine concentrations were detected at the early collection times because of contamination of the oral cavity from the liquid codeine. Codeine concentrations in the 15 min specimens ranged from 690 ng/mL to over 15,000 ng/mL. After the initial 2-h period, the mean codeine saliva concentrations declined at a rate similar to that observed in the plasma, but remained 3 to 4 times greater than the plasma concentrations. During the elimination phase, half-life estimates for codeine in plasma and saliva were found to be equivalent, 2.6 and 2.9 h, respectively. However, the area under the curve (AUC) estimate for codeine in saliva was 13 times greater than the plasma AUC. Contamination of the saliva resulted in elevated saliva/plasma (S/P) concentration ratios for the first 1 to 2 h after drug administration. Consequently, S/P ratios in specimens collected in the first 15 to 30 min ranged from 75 to 2580. However, after the absorption phase, a significant correlation between saliva and plasma concentrations was observed (r = 0.809, p < 0.05) and mean S/P ratios remained constant (mean = 3.7). Although small changes in saliva pH were predicted to produce profound changes in the S/P ratios for codeine, this was not observed in the current study. Therefore, saliva codeine concentrations could be used to estimate plasma concentrations through the use of the S/P ratio once the oral contamination has been eliminated. However, these estimates should be made cautiously. One must ensure that oral contamination is not a factor. Also, as with blood-drug concentrations, considerable intersubject variability was observed.

Can the use of psychoactive drugs in the general adult population be estimated based on data from a roadside survey of drugs and driving?

“…A mean codeine concentration of 7 ng/ml has been found in oral fluid 12 h after oral administration of 30 mg codeine phosphate (11). When using 7 ng/ml as cutoff, the prevalences of use of 30 mg during the last 12 h can be estimated.…”

Oral fluid as an alternative matrix to monitor opiate and cocaine use in substance-abuse treatment patients

“…Disadvantages include variability of salivary flow and pH, and a shorter detection window than urine for active drugs. In addition, specimen collection can have a serious impact on analytical findings and smaller volumes of oral fluid are generally collected (Kato et al, 1993;O'Neal et al, 1999). Furthermore, there are few reports of drug concentration data to guide interpretation of oral fluid test results (Cooper et al, 2005).…”

“…Controlled drug administration studies have investigated the presence and pharmacokinetic characteristics of a number of these drugs in oral fluid (Cone, 1993;Cone et al, 1997;Jenkins et al, 1995;Jufer et al, 2000;Kacinko et al, 2004;Kato et al, 1993;Kim et al, 2002;Kintz et al, 1998;Kopecky et al, 1997;Moolchan et al, 2000;Navarro et al, 2001;O'Neal et al, 1999;Schepers et al, 2003;Skopp et al, 2001;Wang et al, 1994) Furthermore, oral fluid has been successfully applied in criminal justice programs (Yacoubian et al, 2001), workplace (Cone, 2001) and roadside drug testing (DUI) (Peel et al, 1984;Samyn and van Haeren, 2000), but little is known of the usefulness of oral fluid drug monitoring in a population of substance-abuse treatment patients. Schramm et al assessed oral fluid as an alternative matrix for drug testing to serum and urine in volunteers attending a substance abuse treatment program, with self-reported cocaine-use within the previous 24h (Schramm et al, 1993).…”

Place de la salive et des cheveux dans le dépistage d'un usage de stupéfiants en milieu professionnel

“…Les concentrations mesurées sont fonction de la voie d'administration ainsi que du pH salivaire et semblent évo-luer parallèlement aux concentrations sanguines (22,23). Une corrélation supérieure à 90 % entre la salive et les urines a été observée par Niedbala et al (24) en appliquant les valeurs seuil du SAMHSA pour les urines et une valeur de positivité de 10 |ug/l pour un ou plusieurs opiacés présents dans la salive.…”